Definition of the factors regulating the production, secretion and clearance of the alpha and beta subunits of TSH and the gonadotropins is imperative for an understanding of the biosynthesis of complete glycoprotein hormones. We have developed highly sensitive and specific radioimmunoassays for the immunologically common alpha subunits of the human glycoprotein hormones and the beta subunit of human TSH and utilized these assays to demonstrate that there is an increase in pituitary secretion of both free alpha and beta subunits of TSH after administration of thyrotropin releasing hormone in patients with primary hypothyroidism. We now plan to study the regulation of subunits of the glycoprotein hormones by TRH, luteinizing hormone releasing hormone, thyroid hormones, estrogen, and glucocorticoids in patients with hypothyroidism, hyperthyroidism, hypogonadism, and pituitary tumors. Certain pituitary tumors and malignant neoplasms have shown preferential secretion particularly of alpha subunits. Subunits produced by tumors will be evaluated to determine their incidence, regulation, physicochemical, immunologic, and biologic properties in comparison to natural subunits produced by normal pituitary glands using such techniques as gel and ion exchange chromatography, dose-response curves in radioimmunoassay, and recombination ability.